Many normal immune responses require participation by T-cells. T-cell proliferation is controlled by the presence of a polypeptide growth hormone, interleukin 2 (hereinafter IL-2), formerly known as T-cell growth factor (TCGF). See Gillis and Smith, Nature 28: 154 (1977). The mechanism by which IL-2 controls T-cell growth is not completely understood. However, it is known that IL-2 acts on T-cells via a specific, high affinity plasma membrane receptor. In order to continue to divide, IL-2 dependent T-cells must express this receptor and IL-2 must bind to a portion of this receptor. Robb, et al., J. Exp. Med. 154: 1455 (1981). A more complete knowledge of the biochemistry of the IL-2 receptor would foster a better understanding of the interaction between IL-2 and T-cells. To date this has been hampered, at least in part, by the unavailability of IL-2 receptor in purified form.
Leonard, et al, Nature 300: 267 (1982), reported employing a murine monoclonal antibody, designated anti-Tac, to significantly block the binding of radiolabeled IL-2 to the human lymphoma T-cell line, HUT-102. This antibody resulted from immunization of mice with long term cultures of human T-cells. The anti-Tac antibody was reported to bind to a glycoprotein receptor having a molecular weight of about 47,000-53,000 daltons, and also to proteins having molecular weights of about 113,000 and 180,000 daltons. Leonard, et al., suggested that the cell surface determinant (i.e., the 47,000-53,000 molecular weight protein) to which the anti-Tac antibody bound to was the IL-2 receptor.
Robb and Green, J. Exp. Med. 158: 1332 (1983), reported use of anti-Tac antibody in conjunction with mitogen-activated normal lymphocytes to immunoprecipitate a protein having a molecular weight of about 52,000-57,000 daltons. They found that this same protein also bound to IL-2.
Leonard, et al., Proc. Natl. Acad. Sci. USA 80: 6957 (1983), observed that receptors recognized by anti-Tac antibody on HUT-102 cells and on phytohemagglutinin-activated normal T-cells appeared to be larger on reducing gels than on nonreducing gels, thus suggesting the presence of intrachain disulfide bonds. Also, the HUT-102 cell receptor was reported to exhibit an isoelectric point of from 5.5 to 6.0. From post-translational studies, Leonard, et al., suggested that the HUT-102 receptor is composed of a peptide backbone of 33,000 molecular weight that is initially glycosylated by an N-linked mechanism to achieve a 35,000-37,000 molecular weight doublet and then glycosylated by an O-linked mechanism to increase the weight of the molecule by about 13,000-15,000 daltons.